Association between month of birth and melanoma risk: fact or fiction?

Background: Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Methods: Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. Results: In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Conclusions: Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life.

Replacing surrogate measures by direct quantification of ultraviolet radiation exposure in registry-based analyses of seasonality of melanoma diagnoses.

Seasonal variation in melanoma diagnoses has been observed in numerous studies that used calendar time indicators. Depending on the latitude (and altitude) of the study region, the magnitude of seasonal and year-to-year variation of ultraviolet radiation (UVR) is neglected in these studies. An alternative approach comprises the direct incorporation of UVR measurements into such analyses. The aim of this investigation is a comparative evaluation of these approaches. The population-based Bavarian cancer registry recorded 11 901 incident melanoma cases between 2003 and 2008 that were used for the analysis. UVR intensity data for the same period were available from the solar radiation station at Munich-Neuherberg. Negative binomial regression modelling yielded adjusted relative risks (RR) controlled for year of diagnosis and age in 16 subgroups defined by sex, Breslow thickness and localization. Overall, the analyses showed slightly differing yet consistent results for exposure effects in subgroups. Melanoma evolving on the extremities showed the most pronounced association with increasing level of the UV index among men [e.g. RR=1.086, 95% confidence interval (CI) 1.054-1.119, and RR=1.102, 95% CI 1.046-1.161, for thin and thick melanoma on the upper limbs, respectively] and women (e.g. RR=1.088, 95% CI 1.058-1.119, and RR=1.056, 95% CI 1.010-1.103, for thin and thick melanoma on the lower limbs, respectively). Our analysis provides a benchmark for international comparisons and synthesis of epidemiologic evidence of seasonal variability in melanoma diagnoses. Future studies should use direct UVR measures to enable pooling of risk estimates and resolve remaining inconsistencies potentially resulting from latitudinal differences in exposure between international studies.

Vessel transformation in chronic wounds under topical negative pressure therapy: an immunohistochemical analysis.

The underlying physiological mechanism of topical negative pressure (TNP) therapy is not yet completely understood. This prospective clinical study aims to clarify a potential influence of TNP therapy on vessel proliferation and hypoxia in chronic wounds. TNP was applied on chronic wounds of 16 patients (-125 mmHg) to prepare them for a plastic-surgical reconstruction using free or pedicled flaps. Tissue biopsies were taken from the wound edge and wound bed at different time points. All samples were stained with haematoxylin and eosin, hypoxia-induced factor-1α and endothelial cell markers (CD31 and CD34) for the immunohistological analysis of inflammation, hypoxia and vessel proliferation. Between day 5 and day 8 of treatment, a considerable increase in blood vessel density could be observed, reaching a maximum of approximately 200% in contrast to the vessel density prior to treatment. In addition, the number of hypoxic and inflammatory cells was found to be increased at particular time points. This study demonstrates a stimulating effect on vessel proliferation under TNP treatment. TNP appears to support (neo-) angiogenesis and transformation of chronic non-healing wounds in a physiological wound healing process when combined with surgical debridement. This effect underlines the positive influence of TNP in the treatment of chronic wounds as shown by various clinical reports.

Experimental total wrapping of breast implants with acellular dermal matrix: a preventive tool against capsular contracture in breast surgery?

BACKGROUND: Capsular contracture remains a hitherto unsolved complication after implantation of silicone gel-filled breast prostheses. Based on clinical and experimental data, the use of an acellular dermal matrix as a sheath around implants may lead to lesser capsular contracture acting as a proposed biological environment mimicking wound bed tissue. The aim of our study was to analyse the tissue reaction after implantation of silicone prosthesis with and without an envelope of acellular dermal matrix. METHODS: Implantation of 60 silicone prostheses in the back of Lewis rats were carried out, randomly paired taking one rat from group A and one from group B. Group A included implants completely enveloped with xenogenic acellular dermis and group B undraped silicone implants. At 3, 6 and 12 weeks postoperatively, the samples were explanted and subjected to histological and immunohistochemical evaluation. RESULTS: A new myofibroblast tissue layer was identified in proximity to the implant in both groups. The thickness of the layer in group A was continuously thinner than in group B regarding the different explantation time points. Implants completely wrapped with acellular dermal matrix showed significantly lesser inflammatory signs at 3 and 12 weeks after implantation compared to controls. Cell proliferation after 12 weeks was significantly decreased in group A. CONCLUSION: The slight myofibroblast layer and reduced rate of inflammation and proliferation in the treatment group show a positive effect of total acellular dermal matrix envelope and hypothesise the decrease of capsular contracture in long-term periods.

Seasonality of cutaneous melanoma diagnoses: a comprehensive comparison of results in Bavaria and Northern Ireland.

Ultraviolet radiation is an established skin carcinogen. By analysing the seasonality of melanoma diagnoses, the effect of this risk factor can be examined indirectly. However, previous studies yielded conflicting results, because of vastly differing analytical methods and diverse study designs. Therefore, to validate the findings by Chaillol and colleagues based on 3868 melanoma diagnoses from Northern Ireland, we used an identical methodology to examine the seasonal effects on monthly incidences of 11,901 cutaneous malignant melanoma cases registered from 2003 until 2008 in Bavaria, Germany. Multivariable regression models for count data were used to estimate the effect of seasons while taking into account sex, age, year of diagnosis, Breslow thickness and anatomical site. Point and interval estimates of the adjusted relative risks associated with seasons were compared with the findings of the Irish study. Both analyses demonstrated a promoting effect of intermittent ultraviolet radiation on cutaneous melanoma of a thickness of 2 mm or less evolving on the extremities, whereas no seasonality for melanomas on the trunk was evident. Differences were identified with regard to thick melanomas. In the present analysis, only melanomas with a Breslow thickness of more than 2 mm were also found to be associated with season, in particular, the melanomas on the limbs. Hence, in contrast to the data of, and to the interpretation by, Chaillol and colleagues, an effect of ultraviolet radiation on melanoma progression from thin to thick cannot be excluded.

Radiation dose considerations by intra-individual Monte Carlo simulations in dual source spiral coronary computed tomography angiography with electrocardiogram-triggered tube current modulation and adaptive pitch.

OBJECTIVES: To evaluate radiation dose levels in patients undergoing spiral coronary computed tomography angiography (CTA) on a dual-source system in clinical routine. METHODS: Coronary CTA was performed for 56 patients with electrocardiogram-triggered tube current modulation (TCM) and heart-rate (HR) dependent pitch adaptation. Individual Monte Carlo (MC) simulations were performed for dose assessment. Retrospective simulations with constant tube current (CTC) served as reference. Lung tissue was segmented and used for organ and effective dose (ED) calculation. RESULTS: Estimates for mean relative ED was 7.1 ± 2.1 mSv/100 mAs for TCM and 12.5 ± 5.3 mSv/100 mAs for CTC (P < 0.001). Relative dose reduction at low HR (≤60 bpm) was highest (49 ± 5%) compared to intermediate (60-70 bpm, 33 ± 12%) and high HR (>70 bpm, 29 ± 12%). However lowest ED is achieved at high HR (5.2 ± 1.5 mSv/100 mAs), compared with intermediate (6.7 ± 1.6 mSv/100 mAs) and low (8.3 ± 2.1 mSv/100 mAs) HR when automated pitch adaptation is applied. CONCLUSIONS: Radiation dose savings up to 52% are achievable by TCM at low and regular HR. However lowest ED is attained at high HR by pitch adaptation despite inferior radiation dose reduction by TCM. KEY POINTS: • Monte Carlo simulations allow for individual radiation dose calculations. • ECG-triggered tube current modulation (TCM) can effectively reduce radiation dose. • Slow and regular heart rates allow for highest dose reductions by TCM. • Adaptive pitch accounts for lowest radiation dose at high heart rates. • Women receive higher effective dose than men undergoing spiral coronary CT-angiography.